Due to its high behavioral plasticity and capability to adapt to different environmental conditions, Anopheles arabiensis has become one of the most predominant malaria vector species in Africa. This formidable adaptability has paralleled a progressive reduction in the effectiveness of indoor residual spraying and deployment of insecticide-treated nets. The A. arabiensis genome has been rearranged by multiple polymorphic inversions, some of them considered to be instrumental in the expansion of this species across a large array of environmental conditions and in its opportunistic behavior. Although outstanding genomics advances have been achieved in its sister species A. gambiae, A. arabiensis has received little attention. In this proposal, we will use a novel combination of sampling strategies and high-throughput genomic tools to address the role of two widespread chromosomal inversions (2Ra and 3Ra) within the context of local adaptation to differences in humidity for A. arabiensis. For this purpose, we will sample A. arabiensis populations in Burkina Faso, where both inversions are naturally segregating. Further, we will use for the first time high-throughput sequencing of paired-ends reads (Illumina Solexa) to map the breakpoints of these inversions. Conventional procedures at the molecular and computational levels will allow us to characterize breakpoint regions in order to elucidate the molecular mechanisms that originated the two inversions and whether they are associated with position effects. Next, we will investigate the expression patterns across both chromosomal arrangements by using a newly developed microarray platform for A. arabiensis. The resulting portrait of functional differentiation will allow us to compare alternative chromosomal arrangements (inverted and collinear) for both inversions. We will pay special attention to expression divergence in alternative chromosomal arrangements for developmental stages (larva and adults) and tissues (carcasses and head/antenna) to decipher the adaptive response to resting choice and humidity adaptation mediated by these two inversions. Importantly, the expected outcomes will allow to develop molecular tests (e.g. PCR-assays) for monitoring chromosomal arrangements in natural populations of A. arabiensis and will uncover new candidate genes for new genomic vector control measures. PUBLIC HEALTH RELEVANCE: Chromosomal inversion polymorphism has been repeatedly involved in resting preference, feeding behavior and habitat range expansion of the major malaria vectors in Africa, increasing malaria transmission and reducing effectiveness on vector control strategies. Capitalizing on the availability of complete genome sequences and high-throughput molecular technologies, we propose to study two continent widespread inversions (2Ra and 3Ra) that facilitate the adaptation of the proficient malaria vector Anopheles arabiensis to differences in humidity. Our results will allow to understand the genetic basis of th adaptation of Anopheles arabiensis to particular environmental conditions and to develop molecular assays to monitor the presence of the mentioned inversions in the context of seasonal changes of different environmental parameters, which will help in the design of more effective control strategies.